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1yc8

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[[Image:1yc8.gif|left|200px]]
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{{STRUCTURE_1yc8| PDB=1yc8 | SCENE= }}
{{STRUCTURE_1yc8| PDB=1yc8 | SCENE= }}
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'''cAbAn33- Y37V/E44G/R45L triple mutant'''
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===cAbAn33- Y37V/E44G/R45L triple mutant===
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==Overview==
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Heavy chain only antibodies of camelids bind their antigens with a single domain, the VHH, which acquired adaptations relative to classical VHs to function in the absence of a VL partner. Additional CDR loop conformations, outside the canonical loop structures of VHs, broaden the repertoire of the antigen-binding site. The combined effects of part of the CDR3 that folds over the "former" VL binding site and framework-2 mutations to more hydrophilic amino acids, enhance the solubility of VHH domains and prevent VL pairing. cAbAn33, a VHH domain specific for the carbohydrate moiety of the variant surface glycoprotein of trypanosomes, has a short CDR3 loop that does not cover the former VL binding site as well as a VH-specific Trp47 instead of the VHH-specific Gly47. Resurfacing its framework-2 region (mutations Tyr37Val, Glu44Gly and Arg45Leu) to mimic that of a human VH restores the VL binding capacity. In solution, the humanised VHH behaves as a soluble, monomeric entity, albeit with reduced thermodynamic stability and affinity for its antigen. Comparison of the crystal structures of cAbAn33 and its humanised derivative reveals steric hindrance exerted by VHH-specific residues Tyr37 and Arg45 that prevent the VL domain pairing, whereas Glu44 and Arg45 are key elements to avoid insolubility of the domain.
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(as it appears on PubMed at http://www.pubmed.gov), where 15913651 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15913651}}
==About this Structure==
==About this Structure==
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[[Category: Antibody]]
[[Category: Antibody]]
[[Category: Camel antibody]]
[[Category: Camel antibody]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:08:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:35:37 2008''

Revision as of 18:35, 28 July 2008

Image:1yc8.png

Template:STRUCTURE 1yc8

cAbAn33- Y37V/E44G/R45L triple mutant

Template:ABSTRACT PUBMED 15913651

About this Structure

1YC8 is a Single protein structure of sequence from Camelus dromedarius. Full crystallographic information is available from OCA.

Reference

Antigen binding and solubility effects upon the veneering of a camel VHH in framework-2 to mimic a VH., Conrath K, Vincke C, Stijlemans B, Schymkowitz J, Decanniere K, Wyns L, Muyldermans S, Loris R, J Mol Biol. 2005 Jul 1;350(1):112-25. PMID:15913651

Page seeded by OCA on Mon Jul 28 21:35:37 2008

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